The overall objectives of this proposal are to determine the cell population kinetics of malignant and benign human brain tumors; to define the principles of cell population proliferative behavior of human and animal brain tumors in response to therapeutic agents (drugs and radiation); and, based on cell kinetic analysis, to develop treatment regimens that will improve brain tumor therapy. To accomplish these objectives we propose to develop and validate the use of the rapid flow microfluorometry and PDP techniques for determining the kinetics of tumor and normal brain cell populations not only in culture and in our rat model but also in humans. Eight assay systems will be employed where applicable: PLM curves, double autoradiography, stathmokinetic analysis, either alone or combined with a pulse of H3-TdR, FMF analysis either alone or combined with stathmokinetic analysis, PDP analysis and cinemicrography. This systematic attack on the kinetics of perturbed and unperturbed tumor cell populations should lead to the rational development of improved therapeutic regimens for the treatment of malignant brain tumors. FMF analysis offers the possibility that brain tumor therapy could be designed on the basis of immediately available kinetic information obtained from an individual patient's tumor.